Interaction between Levothyroxine and Simethicone
Moderate Absorption

ID DDInter1064 and DDInter1674
Interaction INTERVAL: Concurrent administration of simethicone and/or antacid preparations may decrease the oral bioavailability of levothyroxine. Pharmacologic effects of levothyroxine may be reduced. The exact mechanism of interaction is unknown but may involve nonspecific adsorption of levothyroxine to polyvalent cations, resulting in an insoluble complex that is poorly absorbed from the gastrointestinal tract. Additionally, because gastric acidity is required for adequate levothyroxine absorption, agents that effect intragastric pH may reduce levothyroxine absorption.
Management It is recommended to separate the times of administration of levothyroxine and simethicone and antacids or other antacid-containing preparations (e.g., didanosine buffered tablets or pediatric oral solution) by at least 4 hours. Monitoring of serum TSH levels is recommended. Patients with gastrointestinal or malabsorption disorders may be at a greater risk of developing clinical or subclinical hypothyroidism due to this interaction.
References
Alternative for Levothyroxine -
Alternative for Simethicone -

Potential Metabolism Interactions

Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.